This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We are requesting node hours on the Anton supercomputer in order to determine the tertiary structure of the tetratricopeptide repeat unit in the cargo binding domain of a kinesin motor protein. Preliminary data obtained using the Desmond molecular dynamics software with standard force fields and explicit solvent models suggests that this ~200 residue domain is a "fast-folder" and likely follows the nucleation-condensation folding mechanism. In addition to determining the 3D structure of an important and biologically functional domain, the ensemble of structures obtained from a multi-microsecond simulation will enable a fundamental analysis of the applicability of various protein folding models and provide structural insight into misfolded and semi-folded states that are not accessible to experimental methods. These results will also be utilized to exhaustively validate the suitability of lattice-based mathematical models for describing folding behavior of repeat proteins.